Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE40555
PROVIDER: PRJNA174288 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Effector-Triggered Immunity (ETI) and Pattern-Triggered Immunity (PTI) are well-defined modes of plant immunity triggered by recognition of pathogen effector proteins and microbe-associated molecular patterns, respectively. While ETI and PTI network extensively share signaling components, the shared components are used in different ways, resulting in distinct network properties in the model plant Arabidopsis: immunity is highly robust against network perturbations in ETI but relatively sensitive in PTI. However, the molecular mechanism how the shared network leads to the different properties is not known. Here we show that sustained MAPK activation compensate salicylic acid (SA) signaling. A 12 DNA microarray study using total RNA from Arabidopsis transgenic plants carrying DEX-inducible MKK4DD in Col or sid2-2 background treated with DEX or control.
2014-07-29 | E-GEOD-40547 | biostudies-arrayexpress
Project description:Effector-Triggered Immunity (ETI) and Pattern-Triggered Immunity (PTI) are well-defined modes of plant immunity triggered by recognition of pathogen effector proteins and microbe-associated molecular patterns, respectively. While ETI and PTI network extensively share signaling components, the shared components are used in different ways, resulting in distinct network properties in the model plant Arabidopsis: immunity is highly robust against network perturbations in ETI but relatively sensitive in PTI. However, the molecular mechanism how the shared network leads to the different properties is not known. Here we show that sustained MAPK activation compensate salicylic acid (SA) signaling.
2014-07-29 | GSE40547 | GEO
Project description:The capacity of the brain to elicit sustained remission of hyperglycemia in rodent models of type 2 diabetes (T2D) following intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1) is well established. Here, we show that icv FGF1 injection induces signaling by extracellular signal-regulated kinases 1 and 2 (ERK1/2), members of the mitogen-activated protein kinase (MAPK) family in the hypothalamus, and that this activation persists for at least 24h. Further, we show that in diabetic Lepob/ob mice, this prolonged response is required for the sustained antidiabetic action of FGF1, since it is abolished by sustained (but not acute) pharmacologic blockade of hypothalamic MAPK/ERK signaling. We also demonstrate that FGF1 R50E, a FGF1 mutant that activates FGF receptors but induces only transient hypothalamic MAPK/ERK signaling, elicits transient but not sustained glucose lowering. These data implicate sustained hypothalamic MAPK/ERK signaling in the mechanism underlying diabetes remission induced by icv FGF1.
2021-07-12 | GSE179918 | GEO
Project description:Muller2008 - Simplified MAPK activation Dynamics (Model B)
Simplified mathematical model (model B)
for predicting MAPK signal expression.
This model is described in the article:
Network topology determines
dynamics of the mammalian MAPK1,2 signaling network: bifan
motif regulation of C-Raf and B-Raf isoforms by FGFR and
MC1R.
Muller M, Obeyesekere M, Mills GB,
Ram PT.
FASEB J. 2008 May; 22(5):
1393-1403
Abstract:
Activation of the fibroblast growth factor (FGFR) and
melanocyte stimulating hormone (MC1R) receptors stimulates
B-Raf and C-Raf isoforms that regulate the dynamics of MAPK1,2
signaling. Network topology motifs in mammalian cells include
feed-forward and feedback loops and bifans where signals from
two upstream molecules integrate to modulate the activity of
two downstream molecules. We computationally modeled and
experimentally tested signal processing in the
FGFR/MC1R/B-Raf/C-Raf/MAPK1,2 network in human melanoma cells;
identifying 7 regulatory loops and a bifan motif. Signaling
from FGFR leads to sustained activation of MAPK1,2, whereas
signaling from MC1R results in transient activation of MAPK1,2.
The dynamics of MAPK activation depends critically on the
expression level and connectivity to C-Raf, which is critical
for a sustained MAPK1,2 response. A partially incoherent bifan
motif with a feedback loop acts as a logic gate to integrate
signals and regulate duration of activation of the MAPK
signaling cascade. Further reducing a 106-node ordinary
differential equations network encompassing the complete
network to a 6-node network encompassing rate-limiting
processes sustains the feedback loops and the bifan, providing
sufficient information to predict biological responses.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000664.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2018-01-26 | BIOMD0000000664 | BioModels
Project description:A delicate balance in cellular signaling is required for plants to distinguish mutualist from parasitic organisms in its environment. Mitogen-activated protein kinase (MAPK) cascades are one of the signaling modules that mediate transduction of extracellular microbial signals into appropriate cellular responses. Here, we employ a transgenic system that simulates activation of two pathogen/stress-responsive MAPKs to study release of metabolites and proteins into root exudates. The premise is based on our previous proteomics study that suggests upregulation of secretory processes in this transgenic system. An advantage of this experimental set-up is the direct focus on MAPK-regulated processes without the confounding complications of other signaling pathways activated by exposure to microbes or microbial molecules. Using non-targeted metabolomics and proteomics studies, we show that MAPK activation can indeed drive the appearance of dipeptides, defense-related metabolites and proteins in root apoplastic fluid. However, the relative levels of other compounds in the exudates were decreased. This points to a bidirectional control of metabolite and protein release into the apoplast. The putative roles for some of the identified apoplastic metabolites and proteins are discussed with respect to possible antimicrobial/defense or allelopathic properties. Overall, our findings demonstrate that sustained activation of MAPKs alters the composition of apoplastic root metabolites and proteins, presumably to influence the plant-microbe interactions in the rhizosphere.
2017-08-25 | MTBLS441 | MetaboLights
Project description:Hair follicle formation depends on reciprocal epidermal-dermal interactions and occurs during skin development, but not in adult life. This suggests that the properties of dermal fibroblasts change during postnatal development. To examine this, we used a PdgfraEGFP mouse line to isolate GFP-positive fibroblasts from neonatal skin, adult telogen and anagen skin and adult skin in which ectopic hair follicles had been induced (EF skin) by transgenic epidermal activation of beta-catenin. We also isolated epidermal cells from each mouse. The gene expression profile of EF epidermis was most similar to that of anagen epidermis, consistent with activation of beta-catenin signalling. In contrast, adult dermis with ectopic hair follicles more closely resembled neonatal dermis than adult telogen or anagen dermis. In particular, genes associated with mitosis were upregulated and extracellular matrix-associated genes were downregulated in neonatal and EF fibroblasts. We confirmed that sustained epidermal beta-catenin activation stimulated fibroblasts to proliferate to reach the high cell density of neonatal skin. In addition, the extracellular matrix was comprehensively remodelled, with mature collagen being replaced by collagen subtypes normally present only in developing skin. The changes in proliferation and extracellular matrix composition originated from a specific subpopulation of fibroblasts located beneath the sebaceous gland. Our results show that adult dermis is an unexpectedly plastic tissue that can be reprogrammed to acquire the molecular, cellular and structural characteristics of neonatal dermis in response to cues from the overlying epidermis. We have isolated the following populations of cells from mouse back skin by flow cytometry: 1A) GFP+ WT neonatal dermal fibroblasts, 1B) ItgA6+ WT neonatal epidermal keratinocytes, 2A) GFP+ WT telogen dermal fibroblasts, 2B) ItgA6+ WT telogen epidermal keratinocytes, 3A) GFP+ D2 transient activation (anagen) dermal fibroblasts, 3B) ItgA6+ D2 transient activation (anagen) epidermal keratinocytes, 4A) GFP+ D2 sustained activation (ectopic follicles) dermal fibroblasts, 4B) ItgA6+ D2 sustained activation (ectopic follicles) epidermal keratinocytes
2011-10-12 | E-GEOD-32966 | biostudies-arrayexpress
Project description:The serine/threonine kinase Akt is a central node in cell signaling. While aberrant Akt activation underlies the development of a variety of human diseases, how different patterns of Akt-dependent phosphorylation dictates downstream signaling and phenotypic outcomes remains largely enigmatic. Herein, we performed a systems-level analysis that integrates method advances of optogenetics, mass spectrometry-based phosphoproteomics, and bioinformatics to elucidate how different Akt intensity, durability, and pattern of stimulation activated temporal phosphorylation profiles in vascular endothelial cells. Through the analysis of ~35,000 phosphorylation sites across multiple conditions precisely controlled by light stimulation, we identified a series of signaling circuits that define the sequential downstream cascade of Akt activation and interrogated how Akt signaling cross-talks with growth factor signaling in endothelial cells. Furthermore, our results categorized substrates of kinases that are preferably activated by oscillating, transient, and sustained Akt signals. We validated a list of Akt motif-carrying phosphosites that covaried with Akt phosphorylation across experimental conditions as potential Akt substrates and presented the entire dataset a rich resource for future studies on Akt signaling and dynamics.
2023-06-27 | PXD034957 | Pride
Project description:Urban versus rural residency in northern Tanzania is associated with a pro-inflammatory phenotype which is explained by differences in food- and endogenous-derived metabolites with immune properties.
| EGAS00001004284 | EGA
Project description:Activation of the Mitogen activated protein kinase (MAPK) cascade following Toll-like receptor (TLR) stimulation enables innate immune cells to rapidly activate cytokine gene expression. A balanced response to signals of infectious danger requires that cellular activation is transient. Here, we identify the MAPK phosphatase Dual specificity phosphatase-1 (DUSP1) as an essential endogenous regulator of the inflammatory response to LPS. DUSP1-deficient (DUSP1-/-) bone marrow derived macrophages showed selectively prolonged activation of p38 MAPK and increased cytokine production. Intraperitoneal challenge of DUSP1-/- mice with LPS caused increased lethality and overshooting production of IL-6 and TNF. Transcriptional profiling revealed that DUSP1 controls a significant fraction of LPS-induced genes, that includes IL-6 and IL-10 as well as the chemokines CCL3, CCL4 and CXCL2. In contrast, the expression of the important mediators of endotoxin lethality, IFN? and IL-12, was not significantly altered by the absence of DUSP1. These data together demonstrate a specific regulatory role of DUSP1 in controlling a subset of LPS-induced genes that determines the outcome of endotoxin shock. Experiment Overall Design: Mice were injected intraperitoneally with E. coli LPS (10µg/g bodyweight) and sacrificed 6h later. Total spleen RNA (5 µg) was prepared, labeled and hybridized to Affymetrix MOE430A 2.0 GeneChips according to the manufacturer's instructions. Three biological replicates per condition were analysed. CEL Files were processed for global normalization and generation of expression values using the rma algorithm in the R affy package (www.bioconductor.org).
2007-11-01 | E-GEOD-3565 | biostudies-arrayexpress
Project description:Although targeted inhibition of the MAPK pathway has achieved remarkable patient responses in many cancers with MAPK hyperactivation, the development of resistance has remained a critical challenge. Besides genomic resistance mechanisms, adaptive tumor response also underlies the resistance to targeted MAPK inhibitors. It is being increasingly appreciated that such bypass mechanisms often lead to the activation of many pro-survival kinases, which complicates the rational design of combination therapies. Here we performed global tyrosine phosphoproteomic (pTyr) analyses and demonstrated that targeted inhibition of MAPK signaling in melanoma cells leads to a profound remodeling of the pTyr proteome. Intriguingly, many of these kinases contain a cholesterol binding motif, suggesting that altered cholesterol metabolism might drive, in a coordinated fashion, the activation of these kinases. Indeed, we found a dramatic accumulation of intracellular cholesterol in melanoma cells (with BRAFV600E mutations) and non-small cell lung cancer cells (with KRasG12C mutations) treated with MAPK and KrasG12C inhibitors, respectively. Importantly, depletion of cholesterol not only prevents the MAPK inhibition-induced feedback activation of pTyr singling but also enhances the cytotoxic effects of MAPK inhibitors, both in vitro and in vivo. Taken together, our findings provide the evidence suggesting that cholesterol functions as a master regulator of the tumor adaptive response to targeted MAPK inhibitors. These results also suggest that MAPK inhibitors could be combined with cholesterol-lowering agents to achieve a more complete and durable response in tumors with hyperactive MAPK signaling.
2021-05-11 | PXD021877 | Pride